Exercise and mitochondrial remodeling to prevent age-related neurodegeneration

Abstract

Healthy brain activity requires precise ion and energy management creating a strong reliance on mitochondrial function. Age-related neurodegeneration leads to a decline in mitochondrial function and increased oxidative stress, with associated declines in mitochondrial mass, respiration capacity, and respiration efficiency. The interdependent processes of mitochondrial protein turnover and mitochondrial dynamics, known together as mitochondrial remodeling, play essential roles in mitochondrial health and therefore brain function. This mini-review describes the role of mitochondria in neurodegeneration and brain health, current practices for assessing both aspects of mitochondrial remodeling, and how exercise mitigates the adverse effects of aging in the brain. Exercise training elicits functional adaptations to improve brain health, and current literature strongly suggests that mitochondrial remodeling plays a vital role in these positive adaptations. Despite substantial implications that the two aspects of mitochondrial remodeling are interdependent, very few investigations have simultaneously measured mitochondrial dynamics and protein synthesis. An improved understanding of the partnership between mitochondrial protein turnover and mitochondrial dynamics will provide a better understanding of their role in both brain health and disease, as well as how they induce protection following exercise.

Keywords: brain; exercise; mitochondria; mitochondria remodeling; neurodegeneration.

Figure 1.

Schematic representation of current practices for analysis of mitochondrial remodeling. Aerobic exercise has positive effects on the healthy brain and may help slow or prevent neurodegeneration. A likely site of the positive benefit of aerobic exercise is the mitochondria. Aerobic exercise is known to cause mitochondrial remodeling. However, a current limitation to our understanding of mitochondrial remodeling in the brain is the reliance on static assessments that use markers for both mitochondrial dynamics and protein turnover that also lack cell type specificity. We advocate for additional studies that use methods that assess the dynamic nature of mitochondrial remodeling events. We also stress that studies should focus on the simultaneous assessment of both mitochondrial dynamics and protein turnover. Finally, we need to understand cell type specificity of these responses. Focusing effort on our proposed methodological approaches could accelerate our understanding of the relatively unknown mechanisms through which aerobic exercise positively impacts brain health. This figure was created with Biorender.